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US3329676A - Fused 1, 4-diazepine ring systems - Google Patents

Fused 1, 4-diazepine ring systems Download PDF

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US3329676A
US3329676A US409818A US40981864A US3329676A US 3329676 A US3329676 A US 3329676A US 409818 A US409818 A US 409818A US 40981864 A US40981864 A US 40981864A US 3329676 A US3329676 A US 3329676A
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compound
fused
ring systems
diazepin
compounds
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US409818A
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Stanley C Bell
Scott J Childress
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Wyeth LLC
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American Home Products Corp
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/06—Peri-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
    • C07D219/04—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
    • C07D219/08—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/78—Ring systems having three or more relevant rings
    • C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
    • C07D311/82—Xanthenes
    • C07D311/84—Xanthenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 9
    • C07D311/86—Oxygen atoms, e.g. xanthones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/06—Peri-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/06—Peri-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/02—Ortho- or ortho- and peri-condensed systems
    • C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
    • C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
    • C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
    • C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
    • C07C2603/18—Fluorenes; Hydrogenated fluorenes

Definitions

  • This invention is concerned with compounds having the 5-phenol-1,4-benzodiazepine nucleus to which is attached in the 6-position thereof a divalent element so joined to the S-phenyl substituent in the ortho-position that a new ring is formed.
  • the invention is also concerned with intermediates occurring in the preparation of these compounds.
  • the claimed final products have central nervous system activity, including anticonvulsant and depressant effects and also exhibit mydriatic activity.
  • Z can be a direct bond, a sulfur atom, an oxygen atom, an imino radical, a methylene group, an ethylene group, or an ethylidene group.
  • Y can be hydrogen, halogen, preferably chlorine or bromine, (lower) alkyl or halo(lower) alkyl.
  • A is hydrogen, or acetoxy; n is 0 or 1, except when A is acetoxy in which case it is 0.
  • the starting materials used in the preparation of the claimed compounds are generally known or can be prepared by well-known procedures.
  • the starting N-acetoxy)acetamidoacetyl chloride (II) is prepared by heating hydroxyaminoacetic acid with acetic anhydride, removing the solvent, and heating the residue in methylene chloride with thionyl chloride.
  • the claimed compounds are prepared by reacting an N(acetoxy)- acetamidoacetyl chloride (II) with a fused ring compound (III) which has an amino function and an oxygen function separated by a three carbon atom chain.
  • This reaction is effected by dissolving compound (II) in a solvent such as methylene chloride and adding the resulting solution, at room temperature, to a solution containing compound (III), in a similar solvent.
  • the reaction mixture is filtered, and the filtrate is concentrated to yield a compound of Formula (IV).
  • the latter compound may be obtained also -by an alternate route by treating compound (IV) with ammonia to cause the same to undergo ring closure thereby forming a 2-acetylamino (1,4)diazepin-3-one.
  • this compound can be hydrolyzed conventionally to yield the corresponding 2- amino compound which can be -diazotized to give the above-mentioned 2-hydroxy-( 1,4) diazepin-3-one.
  • Example 1-2- [acetyl(hydroxy) amino] -N-(9-0xoflu0ren- 1 -yl) acetamide, acetate Compound (II) was prepared by heating a mixture of 4.5 g. of hydroxyaminoacetic acid in 60 ml. of acetic anhydride for 15 minutes at The solvent was removed in vacuo and the residue dissolved in 60 ml. of methylene chloride and 14 ml. of thionyl chloride and refluxed for 10 minutes. The solvent was removed in vacuo'and the residue (II) was dissolved in 50 ml. of methylene chloride and added to a solution of 15.0 g.
  • Example 2.2,4-dihydr0-3H-flu0reno [1,9-e,f] (1,4 diazepin-S-one 1 -oxide
  • a mixture of 0.4 g. of 2-[acetyl(hydroxy)amino]-N- (9-oxofluoren-1-yl) acetamide, acetate, 10 ml. of ethanol and 2 ml. of 6 N hydrochloric acid was heated to boiling. The starting material dissolved and soon the product precipitated out. On cooling, there was filtered 01f 0.23 g. of pure product, M.P. 215-217".
  • Example 4.2,4-dihydr0-3H-fluoren0 [1,9-e,f] (1,4 diazepin-S-one A suspension of 1 g. of 2,4-dihydro-3H-fluoreno [1,9-e,f] (1,4)diazepin-3-one l-oxide in 50 ml. of aqueous alcohol and 1 ml. of 6 N HCl is shaken in the presence of 0.5 g. of 5% of palladium on charcoal with H until one mole of hydrogen is consumed. The filtered solution is concentrated in vacuo and neutralized with sodium carbonate. The product 2,4-dihydro-3H-fluoreno[1,9-e,f] (1,4)diazepin-3-one is recrystallized from acetonitrile.
  • the compounds of the present invention can be prepared and administered in a wide variety of oral and parenteral dosage forms, singly, or, in combination with other coacting compounds. They can if desired be associated with a carrier which can be a solid material or a liquid in which the compound is dissolved, dispersed, or suspended.
  • a carrier which can be a solid material or a liquid in which the compound is dissolved, dispersed, or suspended.
  • the solid compositions can take the form of tablets, powders, capsules, pills, or the like, preferably in unit dosage forms for simple administration or precise dosages.
  • the liquid composition can take the form of solutions, emulsions, suspensions, syrups, or eliXirs.
  • Such conventional solid carriers as sucrose, starches, etc., or liquid vehicles such as non-toxic alcohols, glycerine, or the like, may be thus used.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Description

July 4, 1967 S. C BELL ETAL FUSED 1,4-DIAZEPINE RING SYSTEMS Filed Nov. 9, 1964 6 O Q I 0 0 2-0 N U m I i=1 U INVENTORS STANLEY C. B ELL ATTORNEY United States Patent 3,329,676 FUSED 1,4-DIAZEPINE RING SYSTEMS Stanley C. Bell and Scott J. Childress, Philadelphia, Pa., assignors to American Home Products Corporation, New York, N.Y., a corporation of Delaware Filed Nov. 9, 1964, Ser. No. 409,818 4 Claims. (Cl. 260239.3)
This invention is concerned with compounds having the 5-phenol-1,4-benzodiazepine nucleus to which is attached in the 6-position thereof a divalent element so joined to the S-phenyl substituent in the ortho-position that a new ring is formed. The invention is also concerned with intermediates occurring in the preparation of these compounds.
A's determined by standard test procedures in warmblooded animals, the claimed final products have central nervous system activity, including anticonvulsant and depressant effects and also exhibit mydriatic activity.
The claimed final products are represented by the following general formula:
In the above formulae, Z can be a direct bond, a sulfur atom, an oxygen atom, an imino radical, a methylene group, an ethylene group, or an ethylidene group. Y can be hydrogen, halogen, preferably chlorine or bromine, (lower) alkyl or halo(lower) alkyl. A is hydrogen, or acetoxy; n is 0 or 1, except when A is acetoxy in which case it is 0.
The reactions whereby the claimed compounds are prepared are illustrated graphically in the attached figure, to which the Roman numerals in parenthesis in the following description refer.
The starting materials used in the preparation of the claimed compounds are generally known or can be prepared by well-known procedures. Thus the starting N-acetoxy)acetamidoacetyl chloride (II) is prepared by heating hydroxyaminoacetic acid with acetic anhydride, removing the solvent, and heating the residue in methylene chloride with thionyl chloride.
As shown in the accompanying flowsheet, the claimed compounds are prepared by reacting an N(acetoxy)- acetamidoacetyl chloride (II) with a fused ring compound (III) which has an amino function and an oxygen function separated by a three carbon atom chain. This reaction is effected by dissolving compound (II) in a solvent such as methylene chloride and adding the resulting solution, at room temperature, to a solution containing compound (III), in a similar solvent. The reaction mixture is filtered, and the filtrate is concentrated to yield a compound of Formula (IV). Treatment of this compound (IV) with a mineral acid causes the same to undergo ring closure thereby forming the corresponding 2,4-dihydro(1,4) diazepin-3-one l-oxide (V). Compound (V) can be treated conventionally with phosphorus trichloride or with hydrogen in the presence of a catalyst to afford compound (VII). Compound (V) can also be acylated in the 2-position conventionally by heating with an alkanoic an- 3,329,676 Patented July 4, 1967 hydride such as acetic anhydride to form the corresponding 2-acyloxy compound (VI). In turn compound (VI) can be hydrolysed with acid or base to form the corresponding 2-hydroxy(1,4)diazepin-3-one. The latter compound may be obtained also -by an alternate route by treating compound (IV) with ammonia to cause the same to undergo ring closure thereby forming a 2-acetylamino (1,4)diazepin-3-one. In turn, this compound can be hydrolyzed conventionally to yield the corresponding 2- amino compound which can be -diazotized to give the above-mentioned 2-hydroxy-( 1,4) diazepin-3-one.
The accompanying example serve to illustrate specific details of the preparation of the claimed compounds.
Example 1.-2- [acetyl(hydroxy) amino] -N-(9-0xoflu0ren- 1 -yl) acetamide, acetate Compound (II) was prepared by heating a mixture of 4.5 g. of hydroxyaminoacetic acid in 60 ml. of acetic anhydride for 15 minutes at The solvent was removed in vacuo and the residue dissolved in 60 ml. of methylene chloride and 14 ml. of thionyl chloride and refluxed for 10 minutes. The solvent was removed in vacuo'and the residue (II) was dissolved in 50 ml. of methylene chloride and added to a solution of 15.0 g. (2 equiv.) of l-aminofluorenone in 200 ml. of methylene chloride and filtered from the insoluble hydrochloride salt of the starting amine. The filtrate was concentrated to dryness and the residue was recrystallized from acetonitrile giving 9.6 g. (71%) of product, M.P. 173. Further recrystallization from acetonitrile gave a pure compound, M.P. 178- 180.
Analysis.Calcd. for C H N O C, 64.76; H, 4.58; N, 7.95. Found: C, 64.56; H, 4.42; N, 8.01.
Example 2.2,4-dihydr0-3H-flu0reno [1,9-e,f] (1,4 diazepin-S-one 1 -oxide A mixture of 0.4 g. of 2-[acetyl(hydroxy)amino]-N- (9-oxofluoren-1-yl) acetamide, acetate, 10 ml. of ethanol and 2 ml. of 6 N hydrochloric acid was heated to boiling. The starting material dissolved and soon the product precipitated out. On cooling, there was filtered 01f 0.23 g. of pure product, M.P. 215-217".
Analysis.Calcd. for C H N O C, 71.99; H, 4.03; N, 11.20. Found: C, 72.00; H, 3.98; N, 11.13.
A mixture of 1.5 g. of 2,4-dihydro-3H-fluoreno [1,9-e,f] (1,4)diazepin-3-one l-oxide and 40 ml. of acetic anhydride was heated on the steam bath for 1% hours. After cooling, there was filtered off 1.0 g. of crystalline product, M.P. 226227.
Analysis.-Calcd. for C H N O C, H, N, 9.59. Found: C, 69.75; H, 4.02; N, 9.47.
Example 4.2,4-dihydr0-3H-fluoren0 [1,9-e,f] (1,4 diazepin-S-one A suspension of 1 g. of 2,4-dihydro-3H-fluoreno [1,9-e,f] (1,4)diazepin-3-one l-oxide in 50 ml. of aqueous alcohol and 1 ml. of 6 N HCl is shaken in the presence of 0.5 g. of 5% of palladium on charcoal with H until one mole of hydrogen is consumed. The filtered solution is concentrated in vacuo and neutralized with sodium carbonate. The product 2,4-dihydro-3H-fluoreno[1,9-e,f] (1,4)diazepin-3-one is recrystallized from acetonitrile.
Example 5.1-[Z-acetyKhydruxy)aminoacetamido]-4- methyl-thi0xanthene-9-one, acetate This compound, M.P. 204206, was prepared from 3.9 g. of 1-amino-4-methylthioxanthene-9-one and 1.5 g. hydroxyaminoacetic acid according to the procedure of Example 1.
Analysis.-Calcd. for C H N O S: C, 60.29; H, 4.55; N, 7.03; S, 8.05. Found: C, 60.04; H, 4.25; N, 7.19; S 7.9.
Using the appropriate starting compounds, the following products are also prepared as above described. These products are listed in tabular form to avoid unnecessary repetition of experimental details.
Example Formula Z Y 6 IV S H 7 IV 0 H 8 IV NH Cl 9 IV CH2 Br 10 IV CH2C:H2 CH3 11 IV CH=CH H 12 IV CFa 13 V S H 14 V O H 15 V NH Cl 16 V CH2 Br 17 V CHzCHz CH3 18 V CH=OH H 19 V O CFa 20 VI S H 21 VI 0 H 22 VI NH Cl 23 VI CH2 Br 24 VI CH2CH2 CH 25 VI CH -CH H 26 VI 0 CFa Considerable modification is possible in the selection of the particular reactants as well as in the techniques followed without departing from the scope of the invention as claimed below.
The compounds of the present invention can be prepared and administered in a wide variety of oral and parenteral dosage forms, singly, or, in combination with other coacting compounds. They can if desired be associated with a carrier which can be a solid material or a liquid in which the compound is dissolved, dispersed, or suspended. The solid compositions can take the form of tablets, powders, capsules, pills, or the like, preferably in unit dosage forms for simple administration or precise dosages. The liquid composition can take the form of solutions, emulsions, suspensions, syrups, or eliXirs. Such conventional solid carriers as sucrose, starches, etc., or liquid vehicles such as non-toxic alcohols, glycerine, or the like, may be thus used.
What is claimed is:
1. A compound of the formula:
WALTER A. MODANC-E, Primary Examiner.
ROBERT T. BOND, Assistant Examiner.

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1. A COMPOUND OF THE FORMULA:
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Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3417101A (en) * 1964-11-09 1968-12-17 American Home Prod Fused ring compounds
US3466274A (en) * 1964-07-06 1969-09-09 Manuf Prod Pharma Fluoreno-(1,9-ef)-1,4-diazepine-1-oxides and 1,3-diazafluoranthene-1-oxides
US3530116A (en) * 1967-08-21 1970-09-22 Merck & Co Inc 3(4h)-oxo-2h-thiaxantheno (9,9alpha,1-ef)-1,4-diazepin-8,8-dioxides
EP0430114A2 (en) * 1989-11-28 1991-06-05 Hoechst-Roussel Pharmaceuticals Incorporated Hexahydro-1H-quino[4,3,2-ef][1,4]benzoxazepines and related compounds, a process and intermediates for their preparation and their use as medicaments
US5112829A (en) * 1989-11-28 1992-05-12 Hoechst-Roussel Pharmaceuticals Inc. Hexahydro-1H-quino[4,3,2-ef][1,4]benzoxazepines and related compounds
US5843941A (en) * 1993-05-14 1998-12-01 Genentech, Inc. Ras farnesyl transferase inhibitors
US20020107242A1 (en) * 2000-11-03 2002-08-08 American Home Products Corporation Cyclopenta[b][1,4]diazepino[6,7,1-hi]indoles and derivatives
US20020119966A1 (en) * 2000-11-03 2002-08-29 American Home Products Corporation Cycloocta[b][1,4]diazepino[6,7,1-hi]indoles and derivatives
US20020128261A1 (en) * 2000-11-03 2002-09-12 American Home Products Corporation Cyclohepta [b] [1,4] diazepino [6,7, 1-hi] indoles and derivatives
US20040009970A1 (en) * 2002-04-25 2004-01-15 Wyeth [1,4]Diazepino[6,7,1-ij]quinoline derivatives as antipsychotic and antiobesity agents
US20040019040A1 (en) * 2002-04-25 2004-01-29 Wyeth 1,2,3,4,7,8-Hexahydro-6H-[1,4]diazepino[6,7,1-ij]quinoline derivatives as antipsychotic and antiobesity agents
US20040034005A1 (en) * 2002-04-25 2004-02-19 Wyeth [1,4]Diazocino[7,8,1-hi]indole derivatives as antipsychotic and antiobesity agents
US20060110451A1 (en) * 2004-11-05 2006-05-25 Wyeth Formulations of [1,4]diazepino[6,7,1-IJ]quinoline derivatives
US20060111305A1 (en) * 2004-11-05 2006-05-25 Wyeth Metabolites of certain [1,4]diazepino[6,7,1-ij]quinoline derivatives and methods of preparation and use thereof
US20060122385A1 (en) * 2004-11-05 2006-06-08 Wyeth Process for preparing quinoline compounds and products obtained therefrom
US20070027142A1 (en) * 2005-07-26 2007-02-01 Wyeth Diazepinoquinolines, synthesis thereof, and intermediates thereto
US20070167438A1 (en) * 2006-01-13 2007-07-19 Wyeth Treatment of substance abuse
US20070225277A1 (en) * 2006-03-24 2007-09-27 Wyeth Treatment of pain
US20070225279A1 (en) * 2006-03-24 2007-09-27 Wyeth Therapeutic combinations for the treatment of depression
US20070225278A1 (en) * 2006-03-24 2007-09-27 Wyeth Methods for treating cognitive and other disorders
US20090093630A1 (en) * 2007-09-21 2009-04-09 Wyeth Chiral synthesis of diazepinoquinolines

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None *

Cited By (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3466274A (en) * 1964-07-06 1969-09-09 Manuf Prod Pharma Fluoreno-(1,9-ef)-1,4-diazepine-1-oxides and 1,3-diazafluoranthene-1-oxides
US3417101A (en) * 1964-11-09 1968-12-17 American Home Prod Fused ring compounds
US3530116A (en) * 1967-08-21 1970-09-22 Merck & Co Inc 3(4h)-oxo-2h-thiaxantheno (9,9alpha,1-ef)-1,4-diazepin-8,8-dioxides
US5112829A (en) * 1989-11-28 1992-05-12 Hoechst-Roussel Pharmaceuticals Inc. Hexahydro-1H-quino[4,3,2-ef][1,4]benzoxazepines and related compounds
EP0430114A2 (en) * 1989-11-28 1991-06-05 Hoechst-Roussel Pharmaceuticals Incorporated Hexahydro-1H-quino[4,3,2-ef][1,4]benzoxazepines and related compounds, a process and intermediates for their preparation and their use as medicaments
EP0430114A3 (en) * 1989-11-28 1992-01-29 Hoechst-Roussel Pharmaceuticals Incorporated Hexahydro-1h-quino(4,3,2-ef)(1,4)benzoxazepines and related compounds, a process and intermediates for their preparation and their use as medicaments
US5843941A (en) * 1993-05-14 1998-12-01 Genentech, Inc. Ras farnesyl transferase inhibitors
US7271162B2 (en) 2000-11-03 2007-09-18 Wyeth Cycloocta[b][1,4]diazepino[6,7,1-hi]indoles and derivatives
US20020119966A1 (en) * 2000-11-03 2002-08-29 American Home Products Corporation Cycloocta[b][1,4]diazepino[6,7,1-hi]indoles and derivatives
US20020128261A1 (en) * 2000-11-03 2002-09-12 American Home Products Corporation Cyclohepta [b] [1,4] diazepino [6,7, 1-hi] indoles and derivatives
US20020107242A1 (en) * 2000-11-03 2002-08-08 American Home Products Corporation Cyclopenta[b][1,4]diazepino[6,7,1-hi]indoles and derivatives
US20080009480A1 (en) * 2000-11-03 2008-01-10 Wyeth CYCLOPENTA[b][1,4]DIAZEPINO[6,7,1-hi]INDOLES AND DERIVATIVES
US7271164B2 (en) 2000-11-03 2007-09-18 Wyeth Cyclohepta[b][1,4]diazepino[6,7,1,-hi]indoles and derivatives
US6759405B2 (en) 2000-11-03 2004-07-06 Wyeth Cycloocta[b][1,4]diazepino[6,7,1-hi]indoles and derivatives
US6777407B2 (en) 2000-11-03 2004-08-17 Wyeth Cyclopenta[b][1,4]diazepino[6,7,1-hi]indoles and derivatives
US20040229865A1 (en) * 2000-11-03 2004-11-18 Wyeth Cycloocta[b][1,4]diazepino[6,7,1-hi]indoles and derivatives
US20050004101A1 (en) * 2000-11-03 2005-01-06 Wyeth Cyclopenta[b][1,4]diazepino[6,7,1-hi]indoles and derivatives
US6858604B2 (en) 2000-11-03 2005-02-22 Wyeth Cyclohepta[b][1,4]diazepino[6,7,1-hi]indoles and derivatives
US20050054635A1 (en) * 2000-11-03 2005-03-10 Wyeth Cyclohepta[b][1,4]diazepino[6,7,1,-hi]indoles and derivatives
US7271163B2 (en) 2000-11-03 2007-09-18 Wyeth Cyclopenta[b][1,4]diazepino[6,7,1-hi]indoles and derivatives
US20040009970A1 (en) * 2002-04-25 2004-01-15 Wyeth [1,4]Diazepino[6,7,1-ij]quinoline derivatives as antipsychotic and antiobesity agents
US7012089B2 (en) 2002-04-25 2006-03-14 Wyeth [1,4]Diazocino[7,8,1-hi]indole derivatives as antipsychotic and antiobesity agents
US7687620B2 (en) 2002-04-25 2010-03-30 Wyeth Llc [1,4]diazepino[6,7,1-IJ]quinoline derivatives as antipsychotic and antiobesity agents
US7071185B2 (en) 2002-04-25 2006-07-04 Wyeth 1,2,3,4,7,8-hexahydro-6H-[1,4]diazepino[6,7,1-ij]quinoline derivatives as antipsychotic and antiobesity agents
US20060154920A1 (en) * 2002-04-25 2006-07-13 Wyeth 1,2,3,4,7,8-Hexahydro-6H-[1,4]diazepino[6,7,1-ij] quinoline derivatives as antipsychotic and antiobesity agents
US7129237B2 (en) 2002-04-25 2006-10-31 Wyeth [1,4]Diazepino[6,7,1-ij]quinoline derivatives as antipsychotic and antiobesity agents
US20070004707A1 (en) * 2002-04-25 2007-01-04 Ramamoorthy P S [1,4]Diazepino[6,7,1-IJ]quinoline derivatives as antipsychotic and antiobesity agents
US20040019040A1 (en) * 2002-04-25 2004-01-29 Wyeth 1,2,3,4,7,8-Hexahydro-6H-[1,4]diazepino[6,7,1-ij]quinoline derivatives as antipsychotic and antiobesity agents
US20040034005A1 (en) * 2002-04-25 2004-02-19 Wyeth [1,4]Diazocino[7,8,1-hi]indole derivatives as antipsychotic and antiobesity agents
US20060110451A1 (en) * 2004-11-05 2006-05-25 Wyeth Formulations of [1,4]diazepino[6,7,1-IJ]quinoline derivatives
US20060111305A1 (en) * 2004-11-05 2006-05-25 Wyeth Metabolites of certain [1,4]diazepino[6,7,1-ij]quinoline derivatives and methods of preparation and use thereof
US20060122385A1 (en) * 2004-11-05 2006-06-08 Wyeth Process for preparing quinoline compounds and products obtained therefrom
US7781427B2 (en) 2004-11-05 2010-08-24 Wyeth Llc Process for preparing quinoline compounds and products obtained therefrom
US20070027142A1 (en) * 2005-07-26 2007-02-01 Wyeth Diazepinoquinolines, synthesis thereof, and intermediates thereto
US7671196B2 (en) 2005-07-26 2010-03-02 Wyeth Llc Diazepinoquinolines, synthesis thereof, and intermediates thereto
US20070167438A1 (en) * 2006-01-13 2007-07-19 Wyeth Treatment of substance abuse
US20070225277A1 (en) * 2006-03-24 2007-09-27 Wyeth Treatment of pain
US20070225279A1 (en) * 2006-03-24 2007-09-27 Wyeth Therapeutic combinations for the treatment of depression
US20070225278A1 (en) * 2006-03-24 2007-09-27 Wyeth Methods for treating cognitive and other disorders
US20090093630A1 (en) * 2007-09-21 2009-04-09 Wyeth Chiral synthesis of diazepinoquinolines

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